The increased survival of premature infants in modem neonatal intensive care units has caused a resurgence of retinopathy of prematurity (ROP). It is reasoned that as more and smaller premature babies survive, the incidence of visual loss from ROP will continue to increase unless effective treatments are found. Advanced ROP is characterized by a period of unregulated growth of retinal blood vessels. This growth occurs by a process known as angiogenesis, indicating that the new vessels form by an abnormal sprouting of existing vessels. The loss of vision from angiogenesis is not unique to ROP; collectively, ocular disorders with this feature constitute the leading cause of blindness in the U.S. The significance of research aimed at understanding retinal angiogenesis in an animal model of one of these diseases is amplified by the potential of applying the new knowledge to other ocular conditions in which angiogenesis plays a role. The ultimate goal of this project is to develop methods to prevent retinal angiogenesis based upon understanding gained from studies of a rat model of ROP. To this end, four interrelated research projects are proposed: 1) identification of components of the endothelial cell signal pathways by which angiogenesis is initiated, 2) examination of the digestion of extracellular matrix by angiogenic endothelial cells, 3) investigation of the cell attachment mechanisms by which angiogenic endothelial cells migrate, and 4) determination of the precise mechanism through which fluctuating oxygen exposures encourage retinal angiogenesis.